Stent mandrel fixture and method for minimizing coating defects

ABSTRACT

A method of coating a stent using a pressure mandrel is provided.

CROSS REFERENCE

[0001] This is a divisional application of application Ser. No. filed10/254,203 filed on Sep. 24, 2004.

TECHNICAL FIELD

[0002] This invention relates to an apparatus used in the process ofcoating a stent, and more particularly provides a suction stent mandrelfixture and method for minimizing coating defects on stents.

BACKGROUND

[0003] Blood vessel occlusions are commonly treated by mechanicallyenhancing blood flow in the affected vessels, such as by employing astent. Stents act as scaffolding, functioning to physically hold openand, if desired, to expand the wall of affected vessels. Typicallystents are capable of being compressed, so that they can be insertedthrough small lumens via catheters, and then expanded to a largerdiameter once they are at the desired location. Examples in the patentliterature disclosing stents include U.S. Pat. No. 4,733,665 issued toPalmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No.4,886,062 issued to Wiktor.

[0004]FIG. 1 illustrates a conventional stent 10 formed from a pluralityof struts 12. The plurality of struts 12 are radially expandable andinterconnected by connecting elements 14 that are disposed betweenadjacent struts 12, leaving lateral openings or gaps 16 between adjacentstruts 12. Struts 12 and connecting elements 14 define a tubular stentbody having an outer, tissue-contacting surface and an inner surface.

[0005] Stents are used not only for mechanical intervention but also asvehicles for providing biological therapy. Biological therapy can beachieved by medicating the stents. Medicated stents provide for thelocal administration of a therapeutic substance at the diseased site.Local delivery of a therapeutic substance is a preferred method oftreatment because the substance is concentrated at a specific site andthus smaller total levels of medication can be administered incomparison to systemic dosages that often produce adverse or even toxicside effects for the patient.

[0006] One method of medicating a stent involves the use of a polymericcarrier coated onto the surface of the stent. A composition including asolvent, a polymer dissolved in the solvent, and a therapeutic substancedispersed in the blend is applied to the stent by immersing the stent inthe composition or by spraying the composition onto the stent. Thesolvent is allowed to evaporate, leaving on the stent surfaces a coatingof the polymer and the therapeutic substance impregnated in the polymer.

[0007] A shortcoming of the above-described method of medicating a stentis the potential for coating defects. While some coating defects can beminimized by adjusting the coating parameters, other defects occur dueto the nature of the interface between the stent and the apparatus onwhich the stent is supported during the coating process. A high degreeof surface contact between the stent and the supporting apparatus canprovide regions in which the liquid composition can flow, wick, andcollect as the composition is applied. As the solvent evaporates, theexcess composition hardens to form excess coating at and around thecontact points between the stent and the supporting apparatus. Upon theremoval of the coated stent from the supporting apparatus, the excesscoating may stick to the apparatus, thereby removing some of the coatingfrom the stent and leaving bare areas. Alternatively, the excess coatingmay stick to the stent, thereby leaving excess coating as clumps orpools on the struts or webbing between the struts.

[0008] Accordingly, a new stent mandrel fixture is needed to minimizecoating defects.

SUMMARY

[0009] In accordance with one embodiment, an apparatus for supporting astent during the process of applying a coating substance to the stent isprovided, comprising a mandrel having a hollow tubular body and poresdisposed on the surface of the mandrel, the pores extending through thebody; and a vacuum device in fluid communication with the mandrel forextracting the coating substance that is applied to the stent. Theapparatus can also include a coupling for allowing the mandrel to rotatewith respect to the vacuum device. In one embodiment, the apparatusadditionally includes a first member connected to one end of the mandreland a second member connected to the other end of the mandrel, whereinthe mandrel is disposed through a longitudinal bore of the stent. Thestent can be supported by the first and second members of the apparatussuch that the mandrel does not contact an inner surface of the stent.The first member can be moved incrementally closer to the second memberfor securing the stent between the first and second members.

[0010] In accordance with another embodiment, an apparatus is provided,comprising a first member for supporting a first end of a stent; asecond member for supporting a second end of the stent; a third memberconnecting the first member to the second member and extending through alongitudinal bore of the stent, the third member having a longitudinalbore, and the third member having pores on a surface of the thirdmember, the pores extending all the way through the surface to the bore;and a vacuum device in fluid communication with the bore of the thirdmember for applying a vacuum pressure so as to extract any excesscoating substance that is applied to the stent during a process ofcoating the stent. In one embodiment, the first and second members aregenerally coned shaped and capable of penetrating at least partiallyinto the ends of the stent. As a result, when a stent is positioned onthe apparatus, the exterior surface of the third member does not contactthe inner surface of the stent during the application of the coatingsubstance. The coned shaped first and second members can be hollow andin fluid communication with the bore of the third member. The conedshaped ends can include pores disposed on the surface thereof forallowing the vacuum device to extract the coating substance that isdeposited on the first and second members.

[0011] In accordance with another embodiment of the invention, a stentcoating device is provided, comprising: a mandrel for being inserted atleast partially through a longitudinal bore of a stent, the mandrelhaving a hollow tubular body and pores formed on the surface of themandrel, the pores extending all the way through the body; and a vacuumdevice in fluid communication with the mandrel for collecting excesscoating composition that is applied to the stent.

[0012] In accordance with another embodiment, a method of coating astent is provided, comprising: inserting a stent over a mandrel having ahollow tubular body and pores disposed on the surface of the mandrel,the pores extending through the body; applying a coating composition tothe stent; and applying a vacuumed pressure to the hollow tubular bodyfor extracting the coating composition that is applied to the stent. Thecoating composition can be applied by spraying the composition onto thestent. In one embodiment, the stent can be rotated about thelongitudinal axis of the stent. The coating composition can include apolymer dissolved in a solvent and a therapeutic substance optionallyadded thereto. The outer surface of the mandrel can contact the innersurface of the stent. Alternatively, the outer surface of the mandreldoes not contact the inner surface of the stent.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Non-limiting and non-exhaustive embodiments of the presentinvention are described with reference to the following figures, whereinlike reference numerals refer to like parts throughout the various viewsunless otherwise specified.

[0014]FIG. 1 illustrates a conventional stent;

[0015]FIG. 2 illustrates a stent mandrel fixture in accordance with anembodiment of the invention;

[0016]FIG. 3 illustrates an expanded view of stent mandrel fixture ofFIG. 2;

[0017]FIG. 4 illustrates a perspective view of a part of the stentmandrel fixture of FIG. 2;

[0018]FIG. 5 illustrates a stent mandrel fixture according to anotherembodiment of the invention; and

[0019]FIG. 6 illustrates a flowchart of a method for minimizing coatingdefects using the stent mandrel fixture.

DETAILED DESCRIPTION

[0020]FIGS. 2 and 3 illustrate a stent mandrel fixture 20 in accordancewith an embodiment of the invention. Fixture 20 for supporting a stentincludes a support member 22, a mandrel 24, and a lock member 26.Support member 22 can connect to a motor 28A so as to provide rotationalmotion about the longitudinal axis of a stent, as depicted by arrow 30,during the coating process. Another motor 28B can also be provided formoving fixture 20 in a linear direction, back and forth, along a rail32. The type of stent that can be crimped on mandrel 24 is not ofcritical significance. The term stent is broadly intended to includeself- and balloon-type expandable stents as well stent-grafts.

[0021] Stent mandrel fixture 20 is in fluid communication with a vacuumdevice 34 for collecting excess composition that is applied to thestent. Lock member 26 is coupled to vacuum device 34 via a conduit 36. Acoupler 38 allows mandrel fixture 20 to rotate with respect to conduit36 and vacuum device 34.

[0022] Support member 22 includes a flat end 40 that is coupled to afirst end 42 of mandrel 24. In accordance to one embodiment, mandrel 24can be permanently affixed to support member 22. Alternatively, supportmember 22 can include a bore 44 for receiving first end 42 of mandrel24. First end 42 of mandrel 24 can be threaded to screw into bore 44.Alternatively, a non-threaded first end 42 of mandrel 24 can bepress-fitted or friction-fitted within bore 44. Bore 44 should be deepenough so as to allow mandrel 24 to securely mate with support member22. The depth of bore 44 can be over-extended so as to allow asignificant length of mandrel 24 to penetrate bore 44. This would allowthe length of mandrel 24 to be adjusted to accommodate stents of varioussizes.

[0023] Lock member 26 includes a flat end 46 that can be permanentlyaffixed to a second end 48 of mandrel 24 if end 42 of mandrel 24 isdisengagable from support member 22. A bore 50 extends along lock member26 for allowing mandrel 24 to be in fluid communication with vacuumdevice 34. In accordance with another embodiment, mandrel 24 can have athreaded second end 48 for screwing into bore 50. A non-threaded secondend 48 and bore 50 combination can also be employed such that second end48 of mandrel 24 is press-fitted or friction-fitted within bore 50. Lockmember 26 can be incrementally moved closer to support member 22.Accordingly, stents of any length can be securely pinched between flatends 40 and 46 of the support and lock members 22 and 26. A stent neednot, however, be pinched between ends 40 and 46. A stent can be simplycrimped tightly on mandrel 24.

[0024] Mandrel 24, as illustrated by FIG. 4, includes a hollow tubularbody having a bore 52 extending through the body of mandrel 24. Mandrel24 has pores 54 on its surface that are in communication with bore 52.In other words, pores 54 penetrate all the way through the body ofmandrel 24. Bore 52 and pores 54 can be of any suitable size and anynumber of pores 54 can be provided for effectively allowing the coatingcomposition to be vacuumed off of the stent and mandrel 24. Pore sizeand number depend of a variety of factors including the viscosity of thecomposition used, if the composition is in a saturated state or if itincludes particles, and the power of vacuum that is applied to mandrel24. In accordance to one embodiment, ends 40 and 46 may also includepores 54 for extraction of any excess coating composition.

[0025]FIG. 5 illustrates a view of stent mandrel fixture 20 according toanother embodiment of the invention. Support member 22 and lock member26 include coning end portions 40 and 46, instead of flat ends, forpenetrating into ends of stent 10. The coning end portions 40 and 46 cantaper inwardly at an angle Ø₁ of about 15° to about 75°, more narrowlyfrom about 30° to about 60°. By way of example, angle Ø₁ can be about45°. The outer diameter of mandrel 24 can be smaller than the innerdiameter of stent 10, as positioned on fixture 20, so as to prevent theouter surface of mandrel 24 from making contact with the inner surfaceof stent 10. As best illustrated by FIG. 5, a sufficient clearancebetween the outer surface of mandrel 24 and the inner surface of stent10 is provided to prevent mandrel 24 from obstructing the pattern of thestent body during the coating process. By way of example, the outerdiameter of mandrel 24 can be from about 0.010 inches (0.254 mm) toabout 0.017 inches (0.432 mm) when stent 10 has a mounted inner diameterof between about 0.025 inches (0.635 mm) and about 0.035 inches (0.889mm). In this embodiment, contact between stent 10 and fixture 20 islimited as stent 10 only rests on coning ends 40 and 46. Coning ends 40and 46 as well as mandrel 24 can include pores 54 for allowing excesscoating composition to be extracted by vacuum device 34.

[0026] In order to minimize coating defects from forming on stent 10during the coating process, vacuum device 34 applies a suction force tobore 50 of lock member 26 and bore 52 of mandrel 24. The suction forceshould be of a force strong enough to extract the excess coatingmaterial. For example, the suction force could be greater than a 0.1atmosphere pressure difference between the interior of mandrel 24 (i.e.,bore 52) and exterior to mandrel 24. The suction force then pulls excesscoating into vacuum device 34, as indicated by arrow 56, for storage,disposal, or recycling and reapplication of the coating substance.

[0027]FIG. 6 illustrates a flowchart of a method 100 for minimizingcoating defects using suction mandrel fixture 20. First, a stent, suchas stent 10, is mounted (110) on stent mandrel fixture 20. For fixture20 illustrated in FIG. 2, the stent can be crimped directly onto mandrel24. For fixture 20 of FIG. 5, the stent is securely pinched between ends40 and 46 so that the stent does not make contact with mandrel 24. Next,a coating substance is applied (120), for example by spraying, to thestent. The stent can be rotated about the longitudinal axis of the stentand/or moved in a linear direction, back and forth, passed the spraynozzle. During the application (120) of the coating substance and/orafter the application (120) of coating substance, suction force isapplied (130). After suction is applied (130), the excess coating suckedinto the interior of mandrel fixture 20 is collected (140) in vacuumdevice 34. The excess coating can then be recycled and reapplied,stored, or disposed of in an appropriate manner.

[0028] The coating substance can include a solvent and a polymerdissolved in the solvent and optionally a therapeutic substance or adrug added thereto. Representative examples of polymers that can be usedto coat a stent include ethylene vinyl alcohol copolymer (commonly knownby the generic name EVOH or by the trade name EVAL);poly(hydroxyvalerate); poly(L-lactic acid); polycaprolactone;poly(lactide-co-glycolide); poly(hydroxybutyrate);poly(hydroxybutyrate-co-valerate); polydioxanone; polyorthoester;polyanhydride; poly(glycolic acid); poly(D,L-lactic acid); poly(glycolicacid-co-trimethylene carbonate); polyphosphoester; polyphosphoesterurethane; poly(amino acids); cyanoacrylates; poly(trimethylenecarbonate); poly(iminocarbonate); copoly(ether esters) (e.g., PEO/PLA);polyalkylene oxalates; polyphosphazenes; biomolecules, such as fibrin,fibrinogen, cellulose, starch, collagen and hyaluronic acid;polyurethanes; silicones; polyesters; polyolefins; polyisobutylene andethylene-alphaolefin copolymers; acrylic polymers and copolymers; vinylhalide polymers and copolymers, such as polyvinyl chloride; polyvinylethers, such as polyvinyl methyl ether; polyvinylidene halides, such aspolyvinylidene fluoride and polyvinylidene chloride; polyacrylonitrile;polyvinyl ketones; polyvinyl aromatics, such as polystyrene; polyvinylesters, such as polyvinyl acetate; copolymers of vinyl monomers witheach other and olefins, such as ethylene-methyl methacrylate copolymers,acrylonitrilestyrene copolymers, ABS resins, and ethylene-vinyl acetatecopolymers; polyamides, such as Nylon 66 and polycaprolactam; alkydresins; polycarbonates; polyoxymethylenes; polyimides; polyethers; epoxyresins; polyurethanes; rayon; rayon-triacetate; cellulose; celluloseacetate; cellulose butyrate; cellulose acetate butyrate; cellophane;cellulose nitrate; cellulose propionate; cellulose ethers; andcarboxymethyl cellulose.

[0029] “Solvent” is defined as a liquid substance or composition that iscompatible with the polymer and is capable of dissolving the polymer atthe concentration desired in the composition. Examples of solventsinclude, but are not limited to, dimethylsulfoxide, chloroform, acetone,water (buffered saline), xylene, methanol, ethanol, 1-propanol,tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide,cyclohexanone, ethyl acetate, methylethylketone, propylene glycolmonomethylether, isopropanol, isopropanol admixed with water, N-methylpyrrolidinone, toluene, and mixtures and combinations thereof. Thetherapeutic substance or drug can be for inhibiting the activity ofvascular smooth muscle cells. More specifically, the active agent can beaimed at inhibiting abnormal or inappropriate migration and/orproliferation of smooth muscle cells for the inhibition of restenosis.The active agent can also include any substance capable of exerting atherapeutic or prophylactic effect in the practice of the presentinvention. For example, the agent can be for enhancing wound healing ina vascular site or improving the structural and elastic properties ofthe vascular site. Examples of agents include antiproliferativesubstances such as actinomycin D, or derivatives and analogs thereof(manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee,Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin Dinclude dactinomycin, actinomycin IV, actinomycin I₁, actinomycin X₁,and actinomycin C₁. The active agent can also fall under the genus ofantineoplastic, antiinflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, antiallergic andantioxidant substances. Examples of such antineoplastics and/orantimitotics include paclitaxel (e.g., TAXOL® by Bristol-Myers SquibbCo., Stamford, Conn.), docetaxel (e.g., Taxotere®, from Aventis S.A.,Frankfurt, Germany), methotrexate, azathioprine, vincristine,vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin®from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin®from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of suchantiplatelets, anticoagulants, antifibrin, and antithrombins includesodium heparin, low molecular weight heparins, heparinoids, hirudin,argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax™ (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.,Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such asnifedipine), colchicine, fibroblast growth factor (FGF) antagonists,fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (aninhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand nameMevacor® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonalantibodies (such as those specific for Platelet-Derived Growth Factor(PDGF) receptors), nitroprusside, phosphodiesterase inhibitors,prostaglandin inhibitors, suramin, serotonin blockers, steroids,thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), andnitric oxide. An example of an antiallergic agent is permirolastpotassium. Other therapeutic substances or agents which may beappropriate include alpha-interferon, genetically engineered epithelialcells, dexamethasone, and rapamycin.

[0030] While particular embodiments of the present invention have beenshown and described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

What is claimed is:
 1. A method of coating a stent, comprising:inserting a stent over a mandrel having a hollow tubular body and poresdisposed on a surface of the mandrel, the pores extending through thebody; applying a coating composition to the stent; and applying avacuumed pressure to the hollow tubular body for extracting some of thecoating composition that is applied to the stent.
 2. The method of claim1, wherein the coating composition is applied by spraying thecomposition onto the stent.
 3. The method of claim 1, additionallycomprising rotating the stent about the longitudinal axis of the stentduring the application of the vacuumed pressure.
 4. The method of claim1, wherein the coating composition includes a polymer dissolved in asolvent and a therapeutic substance optionally added thereto.
 5. Themethod of claim 1, wherein an outer surface of the mandrel contacts aninner surface of the stent.
 6. The method of claim 1, wherein an outersurface of the mandrel does not contact an inner surface of the stent.7. The method of claim 1, wherein the mandrel includes a support elementto contact a first end of the stent, a lock element to contact a secondend of the stent, the hollow tubular body connecting the support elementto the lock element.
 8. The method of claim 7, wherein the support andlock elements prevent an outer surface of the hollow tubular body frommaking contact with an inner surface of the stent.
 9. The method ofclaim 7, wherein the support element penetrates at least partially intothe first end of the stent and/or wherein the lock element penetrates atleast partially into the second end of the stent.
 10. The method ofclaim 7, wherein the support and/or lock element include a bore in fluidcommunication with the hollow tubular body.
 11. A method of coating astent, comprising: mounting a stent on or over a hollow body havingpores on a surface of the body, the hollow body being in communicationwith a pressure device to receive a pressure; and performing thefollowing acts contemporaneously: applying a coating substance to thestent, rotating the stent about the longitudinal axis of the stent;applying a pressure into the hollow body to modify the coating substancethat is being applied to the stent.
 12. The method of claim 11, whereinan inner surface of the stent is in intimate contact with an outersurface of the hollow body.
 13. The method of claim 11, wherein an innersurface of the stent does not make contact with an outer surface of thehollow body.
 14. A method of coating a stent, comprising: mounting astent on or over a hollow body having pores on a surface of the body,the hollow body being in communication with a pressure device to receivea pressure; applying a coating substance to the stent; applying apressure into the hollow body to modify the coating substance thatapplied to the stent, wherein the application of the pressure isconducted subsequent to the termination of the application of thecoating substance.
 15. The method of claim 14, wherein an inner surfaceof the stent is in intimate contact with an outer surface of the hollowbody.
 16. The method of claim 14, wherein an inner surface of the stentdoes not make contact with an outer surface of the hollow body.
 17. Themethod of claim 14, additionally comprising rotating the stent about thelongitudinal axis of the stent.